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学科主题基础医学
High glucose stimulates GRO secretion from rat microglia via ROS, PKC, and NF-kappa B pathways
Quan, Yi; Du, Jianhai; Wang, Xian
关键词High Glucose Microglia Gro Ros Pkc Nf-kappa b
刊名JOURNAL OF NEUROSCIENCE RESEARCH
2007-11-01
DOI10.1002/jnr.21421
85期:14页:3150-3159
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]CENTRAL-NERVOUS-SYSTEM ; HUMAN ENDOTHELIAL-CELLS ; OXIDATIVE STRESS ; GENE-EXPRESSION ; C-PEPTIDE ; DIABETIC-RETINOPATHY ; CYTOKINE PRODUCTION ; SIGNALING PATHWAYS ; INTERLEUKIN-8 ; HYPERGLYCEMIA
英文摘要

Hyperglycemia causes direct neuronal damage in diabetic encephalopathy. Microglia have been found to be activated in diabetic encephalopathy, presumably mediating and amplifying neuron degeneration. Chemokine IL-8 plays an important role in the pathogenesis of encephalopathy. Therefore, we investigated whether high glucose could activate microglia and stimulate IL-8 secretion and if so, the possible mechanisms that were involved. ELISA results showed that treatment with high glucose (35 mM) compared with treatment with low glucose (10 mM) time-dependently elevated secretion of GRO (the rat ortholog of human IL-8) in primary cultured rat microglia. Real-time PCR results showed GRO mRNA expression also increased in response to high glucose in a time-dependent manner. These effects were specific to high glucose because the osmolality control had no such effect. High-glucose treatment stimulated the formation of ROS, as seen in the DCF fluorescence assay, increased phosphorylation of PKC, as seen in the Western blot analysis, and activated NF-kappa B, as seen in the luciferase reporter assay. In addition, treatment with the ROS scavenger NAC (2 mM) significantly reduced the high glucose-induced phosphorylation of PKC and GRO secretion. Treatment with the PKC activator PMA (10-50 nM) stimulated GRO secretion, and the PKC inhibitors calphostin C (300 nM) or chelerythrine (1 mu M) attenuated the high glucose-induced GRO secretion. Furthermore, the NF-kappa B inhibitors MG132 (10 mu M) or PDTC (5 mu M) completely blocked the high glucose-induced GRO secretion. In conclusion, high glucose induces GRO secretion and mRNA expression in activated rat microglia, which is mediated by the ROS, PKC, and NF-kappa B pathways. High glucose-induced IL-8 production by microglia may contribute to diabetic encephalopathy. (c) 2007 Wiley-Liss, Inc.

语种英语
WOS记录号WOS:000250970100017
引用统计
被引频次:32[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56300
专题北京大学基础医学院
作者单位1.Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100083, Peoples R China
2.Peking Univ, Hosp 3, Minist Educ, Key Lab Mol Cardiovasc Sci,Inst Vasc Med, Beijing 100871, Peoples R China
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Quan, Yi,Du, Jianhai,Wang, Xian. High glucose stimulates GRO secretion from rat microglia via ROS, PKC, and NF-kappa B pathways[J]. JOURNAL OF NEUROSCIENCE RESEARCH,2007,85(14):3150-3159.
APA Quan, Yi,Du, Jianhai,&Wang, Xian.(2007).High glucose stimulates GRO secretion from rat microglia via ROS, PKC, and NF-kappa B pathways.JOURNAL OF NEUROSCIENCE RESEARCH,85(14),3150-3159.
MLA Quan, Yi,et al."High glucose stimulates GRO secretion from rat microglia via ROS, PKC, and NF-kappa B pathways".JOURNAL OF NEUROSCIENCE RESEARCH 85.14(2007):3150-3159.
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